Y.-M. Lin et al. / Tetrahedron Letters 48 (2007) 5531–5534
5533
Table 1. The substrate scope of the catalytic, stereoselective aldehyde
olefination reaction
nitrobenzaldehyde can be carried out either at a lower
temperature (À78 °C, entry 10), or with less catalyst
loading at À20 °C (entry 11) to furnish E-enone 11
O
Me
(R = 4-NO ) in good yields. Thus, we employed 4-nitro-
2
CHO
O
LA*-LB* (4B)
benzaldehyde as the substrate in the control reaction,
which was designed to determine the necessity of cata-
lyst 4B. Indeed, in the absence of catalyst 4B, the reac-
tion was very slow at À20 °C (entry 12). Less than 2%
+
+
iPr
2
NEt
Cl
R
2 2
CH Cl
R
10
11
Entry
ArCHO
0 (R–)
Cat 4B
(mol %)
Temp
(°C)
Time
(h)
E-Enone 11
(% yield)
of enone 11 (R = 4-NO ) was isolated in more than
2
a
1
72 h.
b
1
2
3
4
5
6
7
8
9
H
10
10
10
5
5
5
5
5
5
10
2
À78
À78
À20
À20
À20
À20
À20
À20
À20
À78
À20
À20
20
>20
20
15
16
15
48
48
42
ꢀ10
c
4-Br
4-Br
2-NO
3-NO
4-NO
2-Cl
2-F
4-Cl
4-NO
4-NO
4-NO
0
In summary, we have discovered a new catalytic reac-
tion for converting aldehydes into E enones exclusively,
using acetyl chloride as a latent vinylating reagent for
this olefination reaction. The new Cu(II) catalyst for-
mally converts two molecules of acetyl chloride into
the synthetic equivalent of an ‘acetyl vinyl’ group that
olefinates aldehyde carbonyl groups. The required
Cu(II) complex for this new olefination reaction is easy
to prepare and not air/moisture sensitive. Compared to
triphenylphosphine oxide by-product from the Wittig
reaction, the trialkyl ammonium chloride generated in
this reaction is more environmental friendly and water
soluble that facilitates product purification. Mechanistic
studies of this new catalytic reaction and expanding its
substrate scope to other enolizable aldehydes and
ketones are the ongoing research effort in our
laboratory.
20
53
48
51
34
29
2
2
2
d
15
1
1
1
0
1
2
2
2
2
20
20
>72
60
50
0
<2
a
b
c
Isolated yield.
Average yield from multiple attempts.
5% recovery of aldehyde 10 (R = 4-Br).
9
d
70% recovery of aldehyde 10 (R = 4-Cl).
The substrate scope of this new olefination reaction was
subsequently investigated (Table 1). Initial studies
employing benzaldehyde 10 (R = H) afforded the
expected enone 11 (R = H) in poor yields, inspite of
many attempts and under various conditions (entry 1).
In order to gauge the percent recovery of the starting
material, the nonvolatile 4-bromobenzaldehyde was
employed to replace benzaldehyde as the substrate for
this reaction. Treatment of 4-bromobenzaldehyde 10
Acknowledgments
Acknowledgment is made to the donors of the American
Chemical Society Petroleum Research Fund (PRF
42754-G1) for support of this research. A.N.N. is the re-
cipient of the Undergraduate Summer Research Fellow-
ship, sponsored by the UT Research Office. We are
grateful to Ms. Tamam Baiz of our department for assis-
tance with the manuscript.
(
R = 4-Br) with 10 mol % of catalyst 4B afforded no
enone at À78 °C, but with 95% recovery of aldehyde
0 (R = 4-Br, entry 2). Increasing the reaction tempera-
ture to À20 °C furnished the expected (E)-enone 11
R = 4-Br) in 20% yield (entry 3). However, increasing
1
(
Supplementary data
the reaction temperature further did not improve the
reaction, presumably due to ketene dimerizations.
Experimental procedures, spectral data, and NMR spec-
At À20 °C, aromatic aldehydes having strong electron
withdrawing groups are particularly good substrates
for this catalytic aldehyde olefination reaction. For
nitrobenzaldehydes 10 (R = NO ), 5 mol % of catalyst
2
4
B was sufficient for the reaction. Regardless of the ste-
References and notes
ric properties of the aldehyde carbonyl groups, their cor-
responding trans enones 11 (R = NO ) were produced
2
1. Wittig, G.; Geissler, G. Liebigs Ann. 1953, 580, 44–57.
2. For an excellent overview on carbonyl alkenation meth-
ods, see: (a) Kelly, S. E. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. I, pp 729–817; For an excellent review,
see: (b) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989,
exclusively in good yields (entries 4–6). In contrast, hal-
ogenated benzaldehydes 10 (R = X) required longer
reaction time. Their corresponding enones 11 (R = X)
were produced in poor yields (entries 3, 7–9). The struc-
ture–reactivity relationship of the substrates suggests
that the electronic, rather than the steric property of
the carbonyl group plays a more important role in this
catalytic olefination reaction.
8
9, 863–927.
3
. For mechanistic studies, see: (a) Maryanoff, B. E.; Reitz,
A. B.; Duhl-Emswiler, B. A. J. Am. Chem. Soc. 1985, 107,
2
17–226; (b) Maryanoff, B. E.; Reitz, A. B.; Mutter, M. S.;
Inners, R. R.; Almond, H. R., Jr. J. Am. Chem. Soc. 1985,
07, 1068–1070; (c) Maryanoff, B. E.; Reitz, A. B.; Mutter,
Among the aromatic aldehydes we examined, 4-nitro-
1
benzaldehyde 10 (R = 4-NO ) was the most reactive
M. S.; Inners, R. R.; Almond, H. R., Jr.; Whittle, R. R.;
2
substrate for this new reaction. The olefination of 4-
Olofson, R. A. J. Am. Chem. Soc. 1986, 108, 7664–7678;